Smoking is highly prevalent in the psychiatric population, and hospital admittance usually results in partial or complete smoking cessation. Tobacco use is known to affect the metabolism of certain psychoactive drugs, but whether smoking influences the plasma concentration of tricyclic antidepressants (TCAs) remains unclear. This article investigates the possible effect of smoking on the plasma concentration of TCAs. A systematic review of the literature available on PubMed and EMBASE as of October 2020 was carried out using PRISMA guidelines. Studies reporting plasma concentrations of any TCA in both a smoking and a non-smoking group were included and compared. Ten eligible studies were identified and included. In the eight studies investigating the effect of smoking on amitriptyline and/or nortriptyline, five studies found no significant effect. Two studies investigating the effect of smoking on imipramine found a significant effect, and one study investigating the effect of smoking on doxepin found no significant effect. The majority of studies included in this review were influenced by small study populations and other methodical issues. The effect of smoking on the plasma concentration of TCAs is still not entirely clear. There is a possibility that smoking affects the distribution of TCA metabolites, but this is probably not of clinical importance.

Paroxetine is a highly potent and selective inhibitor of serotonin reuptake, with in vitro potency greater than that of fluoxetine, fluvoxamine, and sertraline. It has little affinity for a wide variety of neurotransmitter receptors, including catecholaminergic or histaminergic systems, in marked contrast to the tricyclic antidepressants. Paroxetine undergoes first-pass metabolism that is partially saturable to give metabolites that are pharmacologically inactive in vivo, unlike those of fluoxetine or sertraline.

Long-term treatment with antidepressants is now an accepted strategy in the management of depression. The demonstration of efficacy in this setting requires specific placebo-controlled trials of patients with recurrent depression studied after an adequate period of euthymia and for a long period of follow-up. This review examines the evidence for the prophylactic efficacy of antidepressant therapy with particular emphasis on the selective serotonin reuptake inhibitor, paroxetine.